Insulin-like growth factor 1 and insulin reduced the binding of 1 2 5 I-labelled epidermal growth factor ( 1 2 5 I-EGF) to Swiss 3T3 cells by 15-20% at 37 o C, but not at 4 o C. Scatchard analysis indicated that IGF-1 and insulin affected the higher-affinity component of EGF binding, an effect previously associated with the activation of protein kinase C. However, the inhibition of 1 2 5 I-EGF binding by IGF-1 and insulin was increased, not reduced, when the cells were treated with high concentrations of phorbol esters to down-modulate protein kinase C. We suggest that IGF-1 and insulin activate a protein kinase with similar or overlapping specificity to that of protein kinase C.